Current treatment options for un-ruptured intracranial aneurysms typically include open clipping, endovascular embolization, or observation. Aneurysms have been shown to resolve after Gamma Knife Radiosurgery (GKRS) in the setting of arteriovenous malformation (AVM) treatment. The reasons for aneurysm involution in GKRS for AVMs are unclear, but could include a direct response to radiation in the aneurysm. We undertook this study to examine the effects of GKRS on an in vivo rabbit aneurysm model. Involution of aneurysms after GKRS could provide a safer and more cost-effective treatment alternative for patients harboring un-ruptured intracranial aneurysms.Ten adult New Zealand white rabbits had aneurysms created with a vein patch graft of the right carotid artery. Nine animals were anesthetized, immobilized and underwent stereotactic magnetic resonance (MR) imaging. The aneurysms were treated with a 25gy to the 50% GKRS isodose. MRI surveillance with volumetric analysis of aneurysm size was performed over a 24 month period. Sacrificed animals at the 24 month time point had histopathological analysis of the aneurysm undertaken for comparison to MRI metrics. The aneurysms were demonstrated to be stable and did not rupture over a three-year observation period (Fig. 1). Clinical shape indices remained constant and demonstrate no significant change over the 24-month period, consistent with no increase of rupture risk following radiosurgery (Fig. 2). The results of the study reveal a 40 percent reduction in aneurysm total volume, internal volume, and surface area over the 24-month period (Fig. 3). Whole aneurysm and blood volume averages decreased with linear trends at rates of 1.7% and 1.6% per month (p<0.001, p<0.002, respectively). Aneurysm wall volume percent increased linearly at a rate of 0.3% per month (p<0.001) and is consistent with histopathological examination. No adverse effects were demonstrated in the proximal untreated left carotid or the underling tissue surrounding the treated right carotid aneurysm. Targeted GKRS is successful in promoting histological and hemodynamic changes to the rabbit carotid aneurysm, linearly reducing size over time. GKRS treatment causes histopathological alterations to the aneurysm wall resulting in volume reduction and decrease in rupture risk. Subsequent studies will aim to test the effects of GKRS dose on a larger sample size in combination with endothelial cell stimulation treatment, moving toward clinical trials for GKRS as a noninvasive treatment alternative for aneurysms.